U.S. patent number 4,271,149 [Application Number 06/077,787] was granted by the patent office on 1981-06-02 for germicidal iodine compositions with enhanced iodine stability.
This patent grant is currently assigned to West Agro-Chemical, Inc.. Invention is credited to Michael Oberlander, Murray W. Winicov.
United States Patent |
4,271,149 |
Winicov , et al. |
June 2, 1981 |
**Please see images for:
( Reexamination Certificate ) ** |
Germicidal iodine compositions with enhanced iodine stability
Abstract
New and improved germicidal iodine compositions are provided in
which iodine levels, in the presence of organic adjuvants
containing at least carbon, hydrogen and oxygen atoms, are
maintained for extended periods of time in the presence of iodide,
through the addition of iodate and control of pH within the range
of pH 5-7.
Inventors: |
Winicov; Murray W. (Woodside,
NY), Oberlander; Michael (Kansas City, MO) |
Assignee: |
West Agro-Chemical, Inc.
(Westwood, KS)
|
Family
ID: |
22140054 |
Appl.
No.: |
06/077,787 |
Filed: |
September 21, 1979 |
Current U.S.
Class: |
424/78.07;
424/78.25 |
Current CPC
Class: |
A01N
59/12 (20130101) |
Current International
Class: |
A01N
59/12 (20060101); A01N 59/12 (20060101); A01N
059/12 (); A61K 031/74 (); A61K 031/79 (); A61K
033/18 () |
Field of
Search: |
;424/78,80,150 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
Primary Examiner: Robinson; Douglas W.
Attorney, Agent or Firm: Thompson, Jr.; Howard E.
Claims
We claim:
1. A germicidal iodine composition comprising an aqueous solution
of elemental iodine in a germicidally effective amount not
exceeding about 1.0% and at least one organic substance which
slowly reacts with iodine selected from the group consisting of
iodine complexing polymers, surface active agents, alcohols,
polyols and water soluble solvents, said organic substance
constituting 1 to 50% by weight of said composition, wherein iodine
loss during extended storage due to such reaction is controlled by
providing in said composition balanced sources of iodide ion in the
range of about 0.025% to 0.5% and iodate ion in the range of about
0.005% to 0.2% while maintaining a pH within the range of pH
5-7.
2. A germicidal iodine composition as defined in claim 1 wherein
the pH is controlled within the range pH 5.5-6.5.
3. A germicidal iodine composition as defined in claim 1, wherein
control of pH is enhanced by including a buffering agent.
4. A germicidal iodine composition as defined in claim 1, wherein
the amount of elemental iodine is within the range of 0.01 to
0.25%.
5. A germicidal iodine composition as defined in claim 1, wherein
said organic substance comprises at least one adjuvant selected
from the group consisting of surface active substances, foam
stabilizers, complexing agents, thickeners and solvents.
6. A germicidal iodine composition as defined in claim 5, wherein
adjuvants are selected to provide a composition adapted for topical
application to animal tissue.
7. A germicidal iodine composition as defined in claim 6, wherein
adjuvants are selected to provide a composition adapted for use as
a hand washing composition.
8. A germicidal iodine composition as defined in claim 6, wherein
adjuvants are selected to provide a composition adapted for use as
a bovine teat dip.
9. A germicidal iodine composition as defined in claim 1, wherein
the iodide ion concentration is in the range of about 0.05% to 0.5%
and the iodate ion concentration is in the range of about 0.005% to
0.2%.
10. A germicidal composition as defined in claim 1, wherein the
iodine concentration is about 0.01 to 0.1%, the iodide ion
concentration is about 0.05 to 0.5%, the iodate ion concentration
is about 0.05 to 0.1%, and the pH is within the range of pH 5.5 to
6.5.
Description
This invention relates to new and improved iodine germicidal
compositions in which iodine levels, in the presence of organic
adjuvants containing at least carbon, hydrogen, and oxygen atoms,
are maintained over a period of time in the presence of iodide,
through the addition of iodate and pH maintenance in the range of
pH 5-7.
The purpose of this invention is to provide iodine compositions of
greatly increased elemental iodine stability on storage, where the
elemental iodine is formulated with adjuvants such as organic
detergents, solvents, foam stabilizers, thickeners, buffering
agents or the like, that contain carbon, hydrogen, and oxygen atoms
(and which may also contain other atoms such as nitrogen,
phosphorus, sulfur, etc.). In such compositions the elemental
iodine concentration almost always decreases on storage, frequently
decreasing much beyond the acceptable amounts allowed for labelling
purposes. This invention teaches how the elemental iodine levels
can be maintained by the addition of iodate and maintaining the pH
in the range of ph 5-7. This teaching is particularly valuable in
situations where it is desirable to maintain elemental iodine at
levels below 1%, and as low as about 0.01%.
The detergent-iodine literature, mostly consisting of patents and
product labels, contains many examples of germicidal iodine
products containing 0.5 to 20% iodine. There are hardly any
instances of iodine products containing only 0.1% iodine or less.
There are two very good reasons for this gap. The first reason is
that almost all iodine products offered for sale are in reality
concentrates of one type or another. The directions for use
ordinarily call for dilution with water, --usually dilutions in the
range of 1:100 to 1:1000 with water, so as to provide anywhere from
a few ppm of titratable iodine to perhaps 150 ppm iodine at the
use-dilution. After use, the diluted product is discarded, since
the iodine content of the dilution is only stable for hours, not
for weeks or months. For any product intended to be used after
dilution with water, it pays to make the product iodine level
concentrated, rather than dilute, so that the product is
"economical" in view of the final use, in order to compete with
other germicidal substances.
The second reason that detergent-iodine products rarely contain
0.1% iodine or less is that it was and is (until now) virtually
impossible to maintain a guaranteed amount of iodine at such a low
level. For example, a typical iodine product with a label statement
guaranteeing 1.6% iodine will ordinarily contain about 1.8% iodine
or more when it is manufactured, and it may drop to as low as 1.5%
iodine two years after it was manufactured. If the same product,
with the same detergent content was prepared with only 0.1% iodine
at the start, the iodine content would probably drop to 0% within a
few weeks, --certainly within a few months, through slow reaction
of the iodine with the organic components of the formulation.
There are certain types of iodine products which are ordinarily not
diluted prior to use--such as hand washing compositions, bovine
teat dip products to prevent mastitis, and products for topical
application. Such products frequently do not require high iodine
content for effectiveness, yet formulators find that they have to
put in much more than is needed so that the iodine that is lost is
an acceptable amount based on the percentage of loss relative to
the amount specified on the label. For example, if the organic
constituents of an iodine product will react with about 0.2% iodine
over the shelf life of the product, and if E.P.A. or F.D.A. label
requirements dictate that the product have no more than 110%, and
no less than 90% of the labelled amount of iodine active
ingredient, then a formulator is forced to set the labelled iodine
level at no less than 1.0%, since only then could he manufacture at
1.10%, and end up as low as 0.9% at the end of the guaranteed shelf
life, a 0.2% drop in iodine content, while remaining within the
regulatory agency requrements. In reality the 1% iodine in the
product could be ten times or more iodine than is necessary for the
purpose of efficacy.
In the case of the bovine teat dip, the extra iodine, over what is
needed for efficacy, is a problem in that it needlessly contributes
to iodine levels in milk through skin absorption or through
improper teat washing before milking.
In the case of a hand washing composition, the extra iodine
contributes to unattractive color, attacks jewelry (rings, etc.) on
the hands, and frequently leaves a temporary yellow color on the
skin.
It is well known that iodate and iodide react in the presence of
hydrogen ions to yield elemental iodine and water according to the
equation:
It is also well known that this reaction is very fast at low pH,
e.g. pH 1, 2, or even 3, and that it is slowed down at higher pH
values, becoming almost non-reactive at pH 7 and above. Certain dry
compositions containing an iodate, an iodide and excess solid acid
have been proposed as a means of providing iodine itself at the
time of solution in water. The purpose of this invention is to use
this reaction to provide very slow release of iodine--so slow that
it has never been used before for this purpose--to counterbalance
the slow loss of iodine in iodine compositions that contain organic
water soluble substances.
The compositions of this invention contain elemental iodine in an
amount that usually does not exceed 1%, but is more generally in
the range of 0.01% to 0.25% iodine; iodide ion (from any source)
preferably in the range of 0.05% to 0.5%; iodate ion (from any
source), at least 0.005%, preferably in the range of 0.05% to 0.1%,
an organic substance or substances (detergent or solvent, for
example) which contains C, H, anc O atoms in an amount from 1 to
50%, and pH control, usually accomplished by the inclusion of a
buffering agent (citrate, phosphate, etc.) capable of maintaining a
pH in the range of 5 to 7.
The maintenance of the pH in the narrow range of 5 to 7 is the
essence, since below pH 5, the reaction of iodate and iodide has
been found to proceed too fast to be of value for the purpose of
this invention and would generate iodine faster than necessary,
resulting in too high an elemental iodine level, too rapid
depletion of iodate, and ultimately no counterbalance of iodine
loss through iodine regeneration.
The range of iodide concentration of this invention is not
characterized by sharp limits. The lower preferred range limit of
0.05% represents an amount which ordinarily must be present in
order to provide a sufficient amount to react with the iodate. The
upper preferred limit provides both a large "reservoir" to be drawn
from, and the higher concentration necessary when large amounts of
iodine have to be replenished, or with higher buffered pH, closer
to pH 7, when a higher iodide concentration is desired to increase
the rate of iodine formation.
The range of iodate ion, from any source, should start at about
0.005%, so that it can provide, ultimately about 0.02% extra iodine
in a formulation. For most practical applications, an amount of
0.05-0.10% can be used. Higher amounts can be used, dictated by
economics.
The organic substance is an integral part of this invention in that
all the uses contemplated concern maintaining the concentration of
elemental iodine in an aqueous medium containing organic substances
such as a solvent, an iodine solubilizer, an iodine complexing
agent, etc., detergent, or the like. Elemental iodine reacts more
or less with all such organic substances which contain carbon,
hydrogen, and oxygen ("C, H, and O"). Unless such C, H, O
containing substance is present, there is no need for this
invention. This invention is applicable to essentially all previous
aqueous "complexed iodine" art typified by the subject matter in
U.S. Pat. Nos. 2,931,777; 2,759,869; 3,028,299; 3,028,300 and many
others.
Examples of solvents containing C, H, and O ordinarily used with
iodine are ethanol, propanol, isopropanol, propylene glycol,
glycerine, polyethylene glycol. These are given by way of
illustration, not limitation.
Examples of surface active agents containing C, H, and O ordinarily
used with iodine are ethoxylates of alkylphenols, of moderate
length alcohols, of polyoxypropylene, anionic detergents that are
sulfated, sulfonated, phosphated, carboxylated etc. These, too, are
given by way of illustration, not limitation.
Similarly, this invention can be practiced with iodine in
combination with other C, H, and O containing substances such as
cationic substances and amphoteric substances. The specific organic
substance containing C, H, and O is of no importance to this
invention. It makes no difference whether the iodine is strongly
complexed, weakly complexed, or not complexed at all.
Rather, the need for this invention will be most apparent for
weakly complexed iodine compositions, since these generally show
greater iodine losses while standing on the shelf compared with
strongly complexed iodine.
EXAMPLE 1
A series of iodine compositions were prepared with and without
addition of iodate. The samples were stored for a time period up to
one week, in glass bottles, at room temperature
(20.degree.-25.degree. C.) and at 50.degree. C. for conventional
accelerated storage to simulate extended storage at room
temperature. As soon as a non-iodate old art composition (e.g. 1A,
2A, etc.) lost all its iodine in the 50.degree. C. oven, the iodate
containing counterpart (e.g. 1B, 2B, etc.) was removed and
analyzed. After the last of the "A" series samples failed, less
than one week from the start of the 50.degree. C. storage, all the
room temperature samples were analyzed and the results
recorded.
(See Table I)
The results indicate a dramatic improvement in iodine stability in
the "B" series compared with the old art "A" series as a direct
result of adding iodate to the formulations over the pH range of
about 6 through 7. The "A" series lost noticeably more iodine than
the "B" series even after only one week at room temperature.
The compositions of Example 1 contain glycerine, propylene glycol,
polyethylene glycol 400 (PEG 400), and citric acid as the C, H, O
containing organic substances that tend to react with iodine. In
this particular example, no surface active substances have been
included so as to show that the new teaching extends beyond
applications to detergent-iodine complexation art.
We have found that the rate at which a given amount of iodide and
iodate react at a particular hydrogen ion concentration is not the
same in the presence of C, H, and O containing substances compared
with the same concentrations of iodide, iodate, and hydrogen ions
in pure water.
TABLE I
__________________________________________________________________________
Ingredient 1A 1B 2A 2B 3A 3B 4A 4B 5A 5B
__________________________________________________________________________
Glycerine 50.0% 50.0% None None None None None None 10.0% 10.0%
Propylene Glycol None None 50.0% 50.0% None None 10.0% 10.0% None
None PEG 400 None None None None 50.0% 50.0% None None None None
Iodine 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% 0.1% Sodium
Iodide 0.25% 0.25% 0.25% 0.25% 0.25% 0.25 0.25% 0.25% 0.25% 0.25%
Sodium Iodate None 0.20% None 0.20% None 0.20% None 0.20% None
0.20% Citric Acid 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0% 1.0%
Sodium Hydroxide qs pH 6.2 pH 6.2 pH 6.7 pH 6.7 pH 6.7 pH 6.7 pH
6.3 pH 6.3 pH pH 6.3 Water qs 100% qs 100% qs 100% qs 100% qs 100%
qs 100% qs 100% qs 100% qs qs 100% Initial Iodine Content 0.10%
0.10% 0.10% 0.10% 0.10% 0.10% 0.10% 0.10% 0.10% 0.10% Iodine
Content Oven Storage 50.degree. C. 0.00% 0.04% 0.00% 0.04% 0.00%
0.07% 0.00% 0.07 0.00% 0.08% Iodine Content Room Temperature (one
week) 0.08% 0.10% 0.08% 0.10% 0.07% 0.10% 0.07% 0.10% 0.08% 0.10%
__________________________________________________________________________
The situation becomes rather complicated in that when C, H, and O
containing substances are present, these substances react with the
iodine already present in the composition. When the iodine
compositions contain organic substances that are more reactive,
iodine losses can be best balanced by
(A) lowering the pH in the range pH 5-7,
(B) using more iodide, and
(C) using more iodate.
These parameters can be varied one at a time, two at a time, or all
three together. When the iodine compositions contain less "C, H, O"
organic substances, or organic substances that are only slightly
reactive with iodine, then less iodide can be used if desired, less
iodate, and a higher pH, in the range 5-7. Within the range of pH
5-7, there is an optimum pH to most closely balance iodine loss
through formation of iodine in situ from the iodide and iodate in
the iodine compositions of this invention. This optimum is usually
within the preferred range, pH 5.5-6.5.
The compositions of Example 1, or similar compositions containing
more or less glycerine, propylene glycol, PEG 400, or the like, are
suitable for use in dipping cows' teats after milking as a mastitis
preventative. The iodine in the composition is less firmly
complexed than in typical iodine teat dip formulations containing
about 1% iodine 0.4% iodide, and about 10% of a nonionic detergent.
Less complexed iodine will kill bacteria faster than more complexed
iodine. More important, the total iodine content in the Example 1
compositions is less than 0.5%, compared with about 1.5% for
conventional 1% elemental iodine teat dips, making the Example 1
compositions less of a hazard with respect to possibly
inadvertently contaminating milk with iodine.
The compositions of Example 1 may be modified by the addition of
thickeners and iodine complexing agents such as ethoxylated
detergents, PVP, quaternary amonium compounds, amphoteric
detergents, etc., to achieve any desired level of iodine
complexing. Whatever the final composition, the desired elemental
iodine level can be maintained through addition of iodate and
maintenance of pH in the range of 5-7.
EXAMPLE 2
A series of iodine compositions were prepared, suitable for hand
washing to remove and kill transient bacteria, with and without
addition of iodate. The samples were stored for two weeks at
ambient temperature (21.degree.-26.degree. C.) and at 35.degree. C.
in glass containers to simulate extended product storage at ambient
temperature. Iodine was determined before and after storage. In
these compositions, it has been found that as little as 0.002%
elemental iodine will surpass the performance of 50 ppm of chlorine
by the A.O.A.C. "Available Chlorine Germicidal Equivalent
Concentration Test". It has been customary to use iodine
compositions for hand washing that contain 0.75 to 1.0% elemental
iodine, obviously a gross excess over the amount needed for killing
transient bacteria. Iodine hand washing compositions containing
about 0.1% elemental iodine or less, will find greater consumer
acceptance since there is less yellow color, less odor, less
staining, etc. For this purpose, an iodine content anywhere from
0.1% to 0.01% elemental iodine is satisfactory. The most suitable
compositions will center around 0.025%, which gives a dark, straw
colored product with an almost colorless lather.
(See Table II)
Composition 2A is not considered as an example of this invention
since there is no iodate present. Rather it represents the prior
art, an example in which the iodine has dropped from 0.050% to
0.002% at ambient temperature (21.degree.-26.degree. C.) after two
weeks. Since there is no iodine present in the 35.degree. C.
sample, this means that the efficacy of this composition can not be
guaranteed past about one month. Composition 2B, with no iodide in
the sample other than the small amount formed from iodine as it
reacts with organic matter, is likewise not suitable for sale. In
other experiments we have noted that at least about 0.025% by
weight of iodide ion must be present in order to be able to keep
iodine generated in a meaningful amount by means of iodate.
Composition 2C is an example showing borderline utility, owing to a
minimum level of iodate. There is only about 0.0088% iodate ion in
this composition, which soon becomes too depleted to serve as a
reserve for satisfactory continued iodine generation. Composition 2
D is shown as an example where either the iodide or iodate
concentration should be lowered a little in order to avoid the
slight iodine excess.
TABLE II
__________________________________________________________________________
Ingredient A B C D E F G H I
__________________________________________________________________________
Lauryl Sulfate, NH.sub.4 Salt 5.0% W/W 5.0% 5.0 5.0 5.0 5.0 5.0 5.0
5.0 Lauric Diethanolamide 2.0% 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0
Iodine 0.05% 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Sodium Iodide
0.25% None 0.25 0.25 0.10 0.25 0.25 0.25 0.25 Sodium Iodate None
0.05 0.01 0.20 0.20 0.05 0.05 0.05 0.05 Citric Acid 1.0% 1.0% 1.0%
1.0% 1.0 1.0 1.0 1.00 None Sodium Hydroxide qs pH 6.5 pH 6.5 pH 6.5
pH 6.5 pH 6.5 pH 6.5 pH 7.0 pH pH 6.5 Water qs 100% 100% 100% to
100% to 100% to 100% to 100% to to 100% Initial Iodine Content
0.05% 0.05% 0.05% 0.05% 0.05% 0.05% 0.05% 0.05% 0.05% Final Iodine
Content Ambient 0.002 0 0.008 0.065 0.037 0.026 0.006 0 0.025
35.degree. C. 0 0 0.002 0.070 0.035 0.020 0.002 0 0.020
__________________________________________________________________________
Alternatively, the pH could be raised to close to pH 7.0.
Compositions 2E and 2F are typical examples of satisfactory
compositions which although not exactly the same strength as
originally made, are stable. Compositions 2G and 2H are a pair to
show that pH 7.0 is borderline and pH 7.5 is useless, even though
the hydrogen ion concentration difference is very small.
Composition 2I, with no buffer added performs as well as its
buffered counterpart, 2F. However, this is only because the pH was
still 6.3 at both temperatures, without the buffering. In
situations where there is the possibility of the pH being
significantly disturbed, buffering is essential. Additional
compositions, not shown here, using lactate, and phosphate buffer,
gave the same results. Below pH 5, it is virtually impossible to
control the generation of iodine from added iodate. In terms of the
purpose of this invention, iodine is generated too rapidly to be of
any use. At pH 5 and above, to pH 7, judicious choice of iodide and
iodate can solve the stability problem.
EXAMPLE 3
A series of iodine compositions were prepared, suitable for teat
dipping of dairy cows, as a mastitis preventative, with and without
the addition of iodate. The samples were stored for two weeks in
glass containers at 50.degree. C. to simulate extended product
storage at ambient temperature, and were analyzed for iodine at the
end of this period.
INGREDIENT
(See Table III)
The compositions of Example 3 which are not covered by this
invention are the compositions with no iodate, namely 3A, 3C, 3E
and 3G. The first composition, 3A, would be acceptable as a product
even with an iodine loss of 0.2% over two weeks at 50.degree. C.,
roughly equivalent to a year at ambient temperature, since it could
be released at 1.1% and it would then fall to 0.9%, an acceptable
loss. Composition 3C could probably not be sold as a teat dip,
since the iodine loss over the accelerated test period was 0.2%, or
40% on a relative basis, compared with the original value.
Compositions E and G are unthinkable as products.
However, the same compositions with iodate levels of 0.05 to 0.20%,
compositions 3B, 3D, 3F and 3H, are distinctly improved from an
elemental iodine stability standpoint; and compositions such as 3F
and 3H would offer special advantage as teat dips with very low
danger of inadvertent milk contamination possibility.
Below pH 5, at pH 4.5 for example, it is not practicable to add
iodate, since iodine concentration in the teat dip formula has been
found to actually increase on standing.
Every detergent or iodine carrier or complexer that is acceptable
as a component in an aqueous elemental iodine composition, can also
be used for the purpose of this invention, and the resultant
composition can be shown to have improved iodine stability after
addition of iodate and pH adjustment in the range pH 5-7.
TABLE III
__________________________________________________________________________
Ingredient A B C D E F G H
__________________________________________________________________________
Pluronic P85 9.56 9.56 9.56 9.56 9.56 9.56 9.56 9.56 Citric Acid
0.5% 0.5 0.5 0.5 0.5 0.5 0.5 0.5 Iodine 1.0% 1.0 0.5 0.5 0.25 0.25
0.10 0.10 HI (100% basis) 0.45 0.45 0.2 0.2 0.1 0.1 0.04 0.04
Sodium Iodate None 0.20 None 0.20 None 0.20 None 0.05 Glycerine
10.0 10.0 10.0 10.0 10.0 10.0 10.0 10.0 Sodium Hydroxide qs pH 5.8
pH 5.8 pH 5.6 pH 5.6 pH 5.6 pH 5.6 pH 5.0 pH 5.0 Water to 100% to
100 to 100 to 100 to 100 to 100 to 100 to 100 Initial Iodine 1.0
1.0 0.5 0.5 0.25 0.25 0.11 0.10 Content* Final Iodine 0.8 1.0 0.3
0.5 0.10 0.25 0.01 0.10 Content* Final pH 5.6 5.6 5.6 5.6 5.6 5.5
5.0 5.0
__________________________________________________________________________
*Samples A D reported to nearest 0.1%; samples E & F reported
to nearest 0.05%; G and H to nearest 0.01%. Pluronic P85: An
ethoxylated polyoxypropylene blood polymer with an average
molecular weight in the range of about 5,000.
Because the nature and amounts of organic compounds containing
carbon, hydrogen and oxygen and of other adjuvants can be so widely
varied, it is difficult to define the invention in terms of
amounts, or ranges of amounts of components. This presents no
problem to those wishing to use this invention as for any
particular iodine composition desired to be marketed the optimum
levels of iodide ion and iodate ion concentrations and the optimum
pH adjustment within the range pH 5-7 can be determined by making a
few comparisons of the type presented herein, particularly in
Example 2. Although looking for iodine stability over an extended
period of months or years, meaningful indications of the long
range, ambient temperature stability are obtainable by "accelerated
aging" as for example storing for two weeks at 50.degree. C., or at
some other temperature and time considered appropriate for the
particular composition and its intended use.
It should also be noted that it is not essential to the successful
practicing of this invention that the iodine level remain the same
throughout an extended period of storage. Rather, what is important
is that any change in iodine concentration be held within the
limits of variation permissible for the particular type
product.
Thus germicidal iodine solutions considered to be within the scope
of the present invention are those in which optimum selections of
iodide and iodate ion concentrations and pH within the pH 5 to 7
range for a particular composition are such that the iodine level
during extended storage will remain within the range of variation
permissible for such composition.
Various changes and modifications in the germicidal iodine
compositions herein disclosed may occur to those skilled in the
art, and to the extent that such changes and modifications are
embraced by the appended claims, it is to be understood that they
constitute part of the present invention.
* * * * *